The revised classification criteria for the antiphospholipid syndrome state that antiphospholipid (aPL) antibodies (lupus anticoagulant LAC and/or anticardiolipin aCL and/or anti-β2 -glycoprotein I ...aβ2 GPI antibodies) should be detected on two or more occasions at least 12 weeks apart. Consequently, classification of patient risk and adequacy of treatment may be deferred by 3 months.
In order to early classify patient risk, we evaluated whether aPL positivity confirmation is related to aPL antibody profiles.
Consecutive patients referred to our center who were initially positive in one or more tests exploring the presence of aPL were tested after 3 months. During a 4-year period, 225 patients were initially positive in one or more tests, and 161 were available for confirmation after 3 months. Patients were classified as triple-positive (n = 54: LAC(+) , aCL(+) , aβ2 GPI(+) , same isotype), double-positive (n = 50: LAC(-) , aCL(+) , aβ2 GPI(+) , same isotype) and single-positive (n = 53: LAC or aCL or aβ2 GPI antibodies as the sole positive test).
Among subjects with triple positivity at initial testing, 98% (53 of 54) had their aPL profile confirmed after 12 weeks. The double-positive and single-positive groups had data confirmed in 42 of 50 (84%) and 23 of 57 (40%) subjects, respectively.
Our results show that high-risk subjects with triple-positive aPL profiles are identified early, at the time of the initial screening tests.
There seems to be a clear correlation between antibodies against domain I (anti-DI) of β2Glycoprotein I and severe clinical profiles in antiphospholipid syndrome (APS) patients. We investigated the ...clinical significance of anti-DI antibodies in a cohort of aPL carriers.
One hundred and five carriers persistently positive for IgG anti-β2Glycoprotein 1 antibodies (a-β2GPI) and/or IgG anticardiolipin (aCL) and/or lupus anticoagulants (LAC) were tested for the presence of anti-DI antibodies using the QUANTA Flash® Beta2GPI-Domain I chemiluminescence immunoassay.
Anti-DI antibodies were detected in 44 aPL carriers (41.9%) and they were significantly associated to triple aPL positivity (LAC plus IgG a-β2GPI plus IgG aCL antibodies). Isolated LAC and a-β2GPI antibodies were significantly associated to anti-DI negative aPL carriers. During a 82.2 month mean follow-up, ten aPL carriers (9.5%) developed a first thrombotic event so becoming APS patients. Anti-DI antibodies, triple aPL positivity, thromboembolic risk factors and autoimmune disorders significantly prevailed in carriers becoming APS. Logistic regression analysis showed that anti-DI positivity was an independent risk factor for thrombosis.
Anti-DI antibody positivity can be considered a new risk factor predictive of the first thrombotic event in aPL carriers, instead, negative anti-DI may be useful to identify low-risk aPL carriers.
•Anti-DomainI antibodies (aDI) have never been evaluated in antiphospholipid antibody carriers.•The clinical significance of aDI was investigated in 105 antiphospholipid antibody carriers.•ADI are an independent risk factor for thrombosis in antiphospholipid antibody carriers.•Negative aDI may be useful to identify low-risk antiphospholipid antibody carriers.
Abstract Triple positivity (positive Lupus Anticoagulant, anticardiolipin and anti β2-glycoptrotein I antibodies) identifies the pathogenic autoantibody (anti Domain I of β2-glycoptroteinI) that is ...present in patients with definite Antiphospholipid Syndrome (APS). This is supported by the fact that aβ2GPI antibodies obtained by affinity purification in these patients possess LA activity. Moreover, patients and carriers of this profile carry a much higher risk of thrombosis and pregnancy loss than APS patients with positivity for only one of the tests. Thus, very different risk categories exist among patients with APS as well as among carriers of aPL. Clinical studies and interventional trials should first take these high risk subjects into consideration.
Abstract Diagnosis of antiphospholipid syndrome (APS) is essentially based on the detection of circulating antiphospholipid (aPL) antibodies. Progress have been made on the standardization of tests ...exploring the presence of aPL as guidelines on coagulation and immunological tests were recently published in the literature. Clinical relevance of aPL profile has come from prospective cohort studies in populations with a homogeneous antibody profile supporting the view that triple positivity is a high risk pattern in patients and carriers. In addition to the classic ones, several other tests have been proposed for the diagnosis of APS. The detection of antibodies directed to domain 1 and 4/5 of β2-Glycoprotein I (β2GP1) were found to be particularly sound. Several issues remain to be addressed. We do not yet know what is the physiological function of β2GP1 and the pathophysiology of thrombosis and pregnancy loss in these patients. Moreover, treatment is poorly defined especially in the case of feared catastrophic APS.
Abstract Background Determination of the three recommended tests for the diagnosis of antiphospholipid syndrome Lupus Anticoagulant (LA), anticardiolipin (aCL) and anti β2-Glycoprotein 1 (aβ2GP1) ...antibodies allow physicians to allocate patients into classification (risk) categories. Objectives To measure antibodies of IgG isotype directed towards Domain 4/5 (Dm4/5) of β2GP1. Patients/Methods. In this cross-sectional study we measured IgG aβ2GP1-Dm4/5 in a group of individuals positive for IgG aβ2GP1 and classified as triple (LAC +, IgG aCL +, IgG aβ2GP1 +, n = 32), double (LAC-, IgG aCL +, IgG aβ2GP1 +, n = 23) or single positive (LA-, IgG aCL-, IgG aβ2GP1 +, n = 10). Results Geometric mean and standard deviation of IgG aβ2GP1 values expressed as Chemiluminescent Units (CU) in triple, double, single positive groups and in 40 healthy individuals were 1795 ± 783, 321 ± 181, 29 ± 8 and 5.0 ± 1.0, respectively (ANOVA p < 0.0001). Geometric mean and standard deviation of IgG aβ2GP1-Dm4/5 expressed as Optical Density (OD) in triple, double and single positive groups and in 40 healthy individuals were 0.16 ± 0.13, 0.16 ± 0.15 and 0.26 ± 0.15, 0.13 ± 0,11, respectively (ANOVA p < 0.002). Individuals in the single positive group, expressed significantly higher values with respect to triple (p = 0.04) and double (p = 0.03) positive groups. Approximate OD cut-off value (99° percentile) calculated in 40 normal control subjects is 0.404. Positivity to IgG aβ2GP1-Dm4/5 according to this cutoff was found in only 5 individuals, 3 in triple positive and 2 in single positive groups and was not associated with thromboembolism. Conclusion Mean level of IgG aβ2GP1-Dm4/5 is higher in single positive group. There is no association between positivity to IgG aβ2GP1-Dm4/5 and thromboembolic events.
Summary Background In Italy, infections with carbapenem-resistant Klebsiella pneumoniae (CRKP) have increased markedly since 2009, creating unprecedented problems in healthcare settings and limiting ...treatment options for infected patients. Aim To assess the attributable mortality due to CRKP in ten Italian hospitals and to describe the clinical characteristics of patients with an invasive CRKP and carbapenem-susceptible K. pneumoniae (CSKP) infection. Methods We conducted a matched cohort study, and calculated crude and attributable mortality for CRKP. The attributable mortality was calculated by subtracting the crude mortality rate of the patients with CSKP from the crude mortality rate of the patients with CRKP. We also described the clinical characteristics of CRKP and CSKP patients and analysed the determinants of mortality by using conditional Poisson regression. Findings The study included 98 patients, 49 with CRKP and 49 with CSKP. CRKP patients had undergone more invasive procedures and also tended to have more serious conditions, measured by higher Simplified Acute Physiology Score II. The attributable mortality of CRKP at 30 days was 41%. CRKP patients were three times more likely to die within 30 days matched incidence rate ratio (mIRR): 3.0; 95% confidence interval (CI): 1.5–6.1. Adjusting for potential confounders, the risk remained the same (adjusted mIRR: 3.0; 95% CI: 1.3–7.1). Conclusion CRKP infection had a marked effect on patient mortality, even after adjusting for other patient characteristics. To control the spread of CRKP we recommend prioritization of control measures in hospitals where CRKP is found.
Objective
To evaluate the relationship between the antiphospholipid profile and clinical characteristics of pregnant women with antiphospholipid syndrome (APS) and neonatal outcome.
Methods
We ...retrospectively considered 109 treated pregnancies of 93 patients with primary APS and reviewed the medical records of their 111 infants. Neonatal outcome was assessed using the following variables: weeks of gestational age at delivery, percentiles of birth weight, Apgar score at 5 minutes, need for cardiopulmonary resuscitation in the delivery room, time in the neonatal intensive care unit, infections, and other neonatal complications. Univariate statistical analysis was performed to evaluate the relationship between APS maternal features and neonatal outcome parameters.
Results
When maternal APS features and variables of infant outcome were analyzed, it was evident that lupus anticoagulant (LAC), triple antiphospholipid positivity, and history of vascular thrombosis were significantly associated with some parameters of a poor infant outcome. History of pregnancy morbidity alone was, instead, significantly correlated to the variables of favorable neonatal outcome.
Conclusion
There seems to be more than one kind of pregnant woman with APS. Even when treated with a second‐line therapy plan, mothers with LAC and/or triple antiphospholipid positivity and/or previous thromboembolism seem to have a high probability of poor neonatal outcome, whereas those with pregnancy morbidity alone, treated with conventional drugs, seem to have a high probability of favorable outcome.
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